DESCRIPTION (provided by investigator): Epilepsy is one of the most prevalent neurological disorder. Patients with epilepsy experience recurrent seizures that can cause a variety of symptoms ranging from muscle stiffness to loss of consciousness. Partial epilepsy is the most common syndrome in adult epilepsy patients and mesial temporal lobe epilepsy (MTLE) is the most common form of partial epilepsy. Epilepsy is characterized by the abnormal synchronization of large numbers of neurons. Current therapeutic agents cannot control seizures in 25% of all epileptic patients. Although electrical stimulation of the brain has been very effective to suppress some symptoms of Parkinson's disease, the level of seizure suppression by stimulation has been limited. The reason for this low therapeutic outcome could be attributed to an inadequate target for stimulation, lack of understanding of the mechanisms and non-optimum stimulation parameters. We propose to develop a method to suppress seizures by applying electrical stimulation to the commissural fiber tract that innervates both hippocampi (major epileptogenic foci in MTLE) from a single electrode location. Specifically, we propose to 1) evaluate the effect of low frequency stimulation 2) determine the effect of high frequency stimulation 3) study the mechanisms of the effect of stimulation, 4) analyze the spatial extent of the suppression/excitation effect in an intact hippocampal in-vitro preparation and 5) suppress seizures in a drug-free genetic model of epilepsy in mice. Current therapeutic agents are incapable of controlling seizure activity in 25% of all epileptic patients. The results of this neuro-technology project should provide valuable insights into the mechanisms underlying seizure suppression with electrical stimulation as well as establishing the preliminary design for an effective neural prosthesis for the control of seizures in patients with epilepsy. PUBLIC HEALTH RELEVANCE: About 3 million people have been diagnosed with epilepsy and the cost to the society is about $12.5B/year. Yet, only 25% of patients can receive some therapeutic benefits from anti-epileptic medication. We propose to develop an alternative therapeutic modality to surgical resection that relies on electrical stimulation of the brain to control seizures.